Random Dermatology MCQ - Merkel cell carcinoma

A 78-year-old fair-skinned man presents with a rapidly growing, firm, violaceous, dome-shaped nodule on his sun-exposed forearm. There is no associated tenderness or pruritus. A biopsy is performed. Histopathology reveals a dermal tumor with sheets of small, blue, round cells with scant cytoplasm and numerous mitotic figures. Which immunohistochemical stain profile is most characteristic of this tumor?

A) S100+, SOX10+, HMB-45-
B) CK20+ (perinuclear dot-like pattern), Synaptophysin+, CD45-
C) CD34+, STAT6+, S100-
D) p63+, CK5/6+, p40+
E) CD45+, CD20+, CD3-

Correct Answer: B) CK20+ (perinuclear dot-like pattern), Synaptophysin+, CD45-

Explanation

This patient has a classic presentation of Merkel cell carcinoma (MCC), a rare but aggressive neuroendocrine carcinoma of the skin.

Key Clinical Features:

• Demographic: Elderly, fair-skinned individuals (Fitzpatrick I/II).

• Location: Sun-exposed areas (head/neck > extremities > trunk).

• Appearance: A rapidly growing, firm, painless, violaceous or red dome-shaped nodule.

• The "AEIOU" clinical mnemonic is helpful:

  • Asymptomatic

  • Expanding rapidly

  • Immunosuppression

  • Older than 50

  • UV-exposed site

Key Histopathological Features:

• "Small blue cell tumor": Dermal infiltrate of monotonous, small, round cells with scant cytoplasm, fine granular chromatin, and numerous mitotic figures.

• Apoptosis and necrosis are common.

Characteristic Immunohistochemistry Profile:

The diagnosis is confirmed with a specific immunostaining pattern:

1. CK20+ (positive): This is a highly characteristic finding. It shows a paramedian dot-like (perinuclear) pattern of staining. This is a hallmark of MCC.

2. Neuroendocrine markers+ (e.g., Synaptophysin, Chromogranin): Confirm the neuroendocrine differentiation of the tumor.

3. CD45- (negative): This is crucial to rule out a hematolymphoid malignancy (e.g., lymphoma), which can also look like a "small blue cell tumor."

4. Merkel cell polyomavirus (MCPyV) large T-antigen: Positive in approximately 80% of cases.

Why Not the Other Options?

• (A) S100+, SOX10+, HMB-45-: This is the profile for melanoma (e.g., desmoplastic melanoma).

• (C) CD34+, STAT6+, S100-: This profile is characteristic of solitary fibrous tumor.

• (D) p63+, CK5/6+, p40+: This is the profile for squamous cell carcinoma and its variants.

• (E) CD45+, CD20+, CD3-: This indicates a B-cell lymphoma. CD45 (LCA) is a pan-leukocyte marker positive in lymphomas and negative in MCC.

Management:

• Wide local excision (often with sentinel lymph node biopsy due to high risk of nodal spread).

• Radiation therapy to the primary site and nodal basin is often indicated due to the tumor's radiosensitivity.

• Immunotherapy (e.g., Avelumab, an anti-PD-L1 antibody) for advanced or metastatic disease.

Prognosis: Aggressive tumor with a high rate of local recurrence and nodal metastasis. Prognosis is strongly correlated with stage at diagnosis.